Ozone oxidative preconditioning reduces nitrite levels in blood serum in LPS: induced endotoxic shock in mice.

OBJECTIVE AND DESIGN: Reactive oxygen species, and also reactive species of nitrogen such as nitric oxide, play an important role in the pathogenesis of peritonitis and septic shock. Ozone oxidative preconditioning (OOP) has shown protective effects in various experimental models of peritonitis in rats and endotoxic shock in mice. Currently, strong evidence is available that this protective effect of OOP is due to its action on the balance between endogenous antioxidants and pro-oxidants, which is favorable for anti-oxidant defense. The aim of this research was to elucidate whether or not OOP is able to reduce nitrite levels in blood serum of mice treated with lipopolysaccharide (LPS). We used an experimental model of endotoxic shock induced by LPS in mice in which the animals were pre-treated with ozone/oxygen mixture for 5 days (once daily), with injection of LPS 24 h thereafter to induce endotoxic shock. RESULTS: Mice pretreated with OOP showed a significant decrease in nitrite levels with all three doses tested [0.2 mg/kg (50.91%), 0.4 mg/kg (47.3%) and 1.2 mg/kg (34.6%)]. CONCLUSIONS: Ozone oxidative preconditioning significantly reduced nitrite levels in blood serum of mice with endotoxic shock induced by LPS. We propose that OOP merits further testing in studies as a potential alternative treatment to reduce nitrite levels in patients with sepsis syndrome and septic shock.

Ozone/oxygen mixture modifies the subcellular redistribution of Bax protein in renal tissue from rats treated with cisplatin.

BACKGROUND: Cellular events in cisplatin-mediated nephrotoxicity include apoptosis induction, decreased protein synthesis, changes in the subcellular redistribution of Bax mitochondrial dysfunction, DNA injury, increased lipid peroxidation, depletion of glutathione and decrease in enzymatic activity of renal antioxidant enzymes. In previous papers we have shown that intra-rectal (i.r.) ozone/oxygen mixture protected and induced a significant recovery in cisplatin-induced renal damage and was related to a significant increase in the antioxidant system in renal tissue. METHODS: This study was undertaken to examine the effect of the ir applications of ozone/oxygen mixture in the renal expression pattern of Bax proteins in rats treated with cisplatin. A group of male Sprague-Dawley rats was pretreated with 15 i.r. applications of ozone/oxygen (1.1 mg/kg) before intraperitoneal injection of cisplatin (6 mg/kg). Another group was treated with five i.r. applications of ozone/oxygen mixture after cisplatin administration. Serum creatinine was measured thereafter. Subcellular distribution of Bax in renal tissue was analyzed by immunohistochemistry. RESULTS: Ozone pretreatment prevented the increase in serum creatinine levels and completely inhibited the acute tubular necrosis induced by cisplatin in renal tissue, diminishing the expression of Bax. Ozone treatment after cisplatin application reduced the increase in serum creatinine levels and the renal necrosis, inducing a lesser decrease of the Bax expression in cisplatin-treated kidneys. CONCLUSIONS: Expression of Bax in renal tissue seems to play an important role in the protection and recovery in cisplatin-nephrotoxicity achieved by ozone/oxygen mixture.

Ozone therapy on rats submitted to subtotal nephrectomy: role of antioxidant system.

Chronic renal failure (CRF) represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy). Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg) for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks). Renal plasmatic flow (RPF), glomerular filtration rate (GFR), the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function) in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group) showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP) figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD) and catalase (CAT) showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone rectal administrations produced a delay in the advance of the disease, protecting the kidneys against vascular, hemorheological, and oxidative mechanisms. This behavior suggests ozone therapy has a protective effect on renal tissue by downregulation of the oxidative stress shown in CRF.

Lipid peroxides and antioxidant enzymes in cisplatin-induced chronic nephrotoxicity in rats.

Cisplatin (CDDP), an anticancer drug, induces remarkable toxicity in the kidneys of animals and humans and it has been well documented that reactive oxygen species and the renal antioxidant system are strongly involved in acute renal damage induced by CDDP. The aim of the present study was to investigate whether or not the renal antioxidant system plays also an important role in chronic renal damage induced by repeated doses of CDDP (1 mg/kg intraperitoneally twice weekly during 10 weeks in rats). In order to elucidate it, serum creatinine and urea levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS) content, as well as renal superoxide dismutase and glutathione peroxidase activities were measured in the kidney homogenates of chronically CDDP-treated rats and additionally histological studies were performed in the rat kidneys. The chronic treatment with CDDP induced a significant increase in creatinine and urea levels in serum, but the other parameters mentioned above were not significantly modified as compared to the values in nontreated rats. Taking into account these results, we conclude that chronic CDDP administration induces also severe nephrotoxicity, in contrast to CDDP acute application, without any significant modification in the activity of relevant antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, renal glutathione and lipid peroxides, by which the role of the antioxidant system in chronic nephrotoxicity induced by CDDP in rats is uncertain.

Lipid Peroxides and Antioxidant Enzymes in Cisplatin-Induced Chronic Nephrotoxicity in Rats

Cisplatin (CDDP), an anticancer drug, induces remarkable toxicity in the kidneys of animals and humans and it has been well documented that reactive oxygen species and the renal antioxidant system are strongly involved in acute renal damage induced by CDDP. The aim of the present study was to investigate whether or not the renal antioxidant system plays also an important role in chronic renal damage induced by repeated doses of CDDP (1mg/kg intraperitoneally twice weekly during 10 weeks in rats). In order to elucidate it, serum creatinine and urea levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS) content, as well as renal superoxide dismutase and glutathione peroxidase activities were measured in the kidney homogenates of chronically CDDP-treated rats and additionally histological studies were performed in the rat kidneys. The chronic treatment with CDDP induced a significant increase in creatinine and urea levels in serum, but the other parameters mentioned above were not significantly modified as compared to the values in nontreated rats. Taking into account these results, we conclude that chronic CDDP administration induces also severe nephrotoxicity, in contrast to CDDP acute application, without any significant modification in the activity of relevant antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, renal glutathione and lipid peroxides, by which the role of the antioxidant system in chronic nephrotoxicity induced by CDDP in rats is uncertain(AU)

Cisplatino (CDDP), un fármaco contra el cáncer, induce notables de toxicidad en los riñones de los animales y los seres humanos y ha sido bien documentado que las especies reactivas de oxígeno y el sistema antioxidante renal están fuertemente implicados en el daño renal aguda inducida por CDDP. El objetivo del presente estudio fue investigar si el sistema antioxidante renal desempeña también un papel importante en el daño renal crónica inducida por dosis repetidas de CDDP (1 mg / kg por vía intraperitoneal dos veces a la semana durante 10 semanas en ratas). Con el fin de aclarar que, la creatinina sérica y los niveles de urea, renal y ácido tiobarbitúrico glutatión sustancias de reacción (TBARS) de contenidos, así como insuficiencia renal superóxido dismutasa y glutation peroxidasa actividades se midieron en el homogenado de riñón crónica CDDP-ratas tratadas y además histológico se han realizado estudios en la rata riñones. El tratamiento crónico con CDDP indujo un aumento significativo de los niveles de urea y creatinina en suero, pero los demás parámetros mencionados más arriba no se modificaron significativamente en comparación con los valores de nontreated ratas. Teniendo en cuenta estos resultados, concluimos que la administración crónica CDDP también induce nefrotoxicidad grave, en agudo contraste con CDDP solicitud, sin ninguna modificación significativa en la actividad de las enzimas antioxidantes como la superóxido dismutasa y la glutatión peroxidasa, glutatión renal y peróxidos lípidos, por que el papel del sistema antioxidante en la nefrotoxicidad crónica inducida por CDDP en ratas es incierto

Effects of ozone oxidative preconditioning on TNF-alpha release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock.

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-alpha levels and as a modulator of oxidative stress on hepatic tissue in entodoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-alpha was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-alpha levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-alpha levels in a dose-dependent manner. Statistically significant decreases in TNF-alpha levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78%), 0.4 (98%), and 1.2 (99%). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-alpha production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems.

Effects of Ozone Oxidative Preconditioning on TNF-¦Á Release and Antioxidant-Prooxidant Intracellular Balance in Mice During Endotoxic Shock

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-¦Á levels and as a modulator of oxidative stress on hepatic tissue in entodoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-¦Á was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-¦Á levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-¦Á levels in a dose-dependent manner. Statistically significant decreases in TNF-¦Á levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78percent), 0.4 (98 percent), and 1.2 (99 percent). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-¦Á production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems(AU)

El ozono es un oxidante preacondicionamiento profil¨¢cticos, que favorece el equilibrio prooxidant antioxidantes para la preservaci¨®n de estado redox celular por el aumento de los sistemas antioxidantes end¨®genos en tanto in vivo como in vitro modelos experimentales. Nuestro objetivo es analizar el efecto oxidante del ozono preacondicionamiento en suero los niveles de TNF-¦Á y como modulador del estr¨¦s oxidativo en el tejido hep¨¢tico en entodoxic choque modelo (ratones tratados con lipopolisac¨¢rido (LPS)). Ozono y ox¨ªgeno gaseoso mezcla que se administr¨® por v¨ªa intraperitoneal (0,2, 0,4 y 1,2 mg / kg) una vez al d¨ªa durante cinco d¨ªas antes de LPS (0,1 mg / kg, intraperitoneal). TNF-¦Á se midi¨® por la citotoxicidad de las c¨¦lulas L-929. Par¨¢metros bioqu¨ªmicos, como las materias ¨¢cido tiobarbit¨²rico (TBARS), la actividad enzim¨¢tica de la catalasa, glutation peroxidasa y glutati¨®n S-transferasa se midieron en el tejido hep¨¢tico. Una hora despu¨¦s de la inyecci¨®n de LPS hubo un aumento significativo en los niveles de TNF-¦Á en suero de rat¨®n. Ozono y ox¨ªgeno gaseoso mezcla suero reducido los niveles de TNF-¦Á en una manera dosis-dependiente. Disminuciones estad¨ªsticamente significativas en los niveles de TNF-¦Á despu¨¦s de la inyecci¨®n de LPS se observaron en ratones pretratados con ozono intraperitoneal aplicaciones en 0,2 (78por ciento), 0,4 (98 por ciento) y 1,2 (99 por ciento). Tambi¨¦n un aumento significativo en el contenido de TBARS se observ¨® en el tejido hep¨¢tico de ratones tratados con LPS, mientras que la actividad enzim¨¢tica de la glutati¨®n S-transferasa y glutati¨®n peroxidasa disminuy¨®. Sin embargo, en la capa de ozono, los animales tratados una disminuci¨®n significativa en el contenido de TBARS se apreciaba, as¨ª como un aumento en la actividad de enzimas antioxidantes. Estos resultados indican que el ozono preacondicionamiento oxidativo ejerce efectos inhibidores sobre la producci¨®n de TNF..........................

Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we show the protective effect of ozone oxidative preconditioning against cisplatin-induced renal dysfunction in rats. Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-pro-oxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in various in vivo and in vitro experimental models. AIMS: To analyze the protective role of ozone oxidative preconditioning against cisplatin-induced nephrotoxicity. METHODS: Male Sprague-Dawley rats were pretreated with 15 intrarectal applications of ozone/oxygen mixture at 0.36, 0.72, 1.1, 1.8 and 2.5 mg/kg before cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were extracted and analyzed 5 days after cisplatin treatment for determinations of the renal content of glutathione, thiobarbituric acid-reactive substances, renal concentration and enzymatic activities of catalase, superoxide dismutase and glutathione peroxidase. RESULTS: Ozone pretreatment prevented the increase in serum creatinine levels, the glutathione depletion and the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric acid-reactive substances was decreased by ozone therapy. These protective effects of ozone were dose dependent. CONCLUSIONS: Intrarectal ozone therapy prevented effectively the renal antioxidant unbalance induced by cisplatin treatment.

Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats.

BACKGROUND: Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species AIMS: To analyze the effect of ozone administration after cisplatin-induced acute nephrotoxicity. METHODS: Male Sprague-Dawley rats were treated with five intra-rectal applications of ozone/oxygen mixture at 0.36, 1.1 and 1.8 mg/kg after cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were taken off 5 days after cisplatin treatment. Creatinine was measured in the serum and the activities of antioxidant enzymes and thiobarbituric acid reactive substances and glutathione content were analyzed in renal homogenate. RESULTS: Ozone treatment diminished the increase in serum creatinine levels, the glutathione depletion and also reversed the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric reactive substances was decreased by ozone/oxygen mixture applied after cisplatin. CONCLUSION: Intrarectal applications of ozone reversed the renal pro-oxidant unbalance induced by cisplatin treatment by the way of stimulation to some constituents of antioxidant system in the kidney, and thereby it decreased the renal damage.

Inhibition of tumor necrosis factor-alpha release during endotoxic shock by ozone oxidative preconditioning in mice.

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in both in vivo and in vitro experimental models. The aim of this study was to analyze the effect of ozone oxidative preconditioning on the level of tumor necrosis factor-alpha (TNF-alpha) in the serum of mice treated with lipopolysaccaride (LPS). Pretreatment with an ozone/oxygen gaseous mixture was administered intraperitoneally (0.2, 0.4 and 1.2 mg/kg) or by rectal application (0.2 and 0.4 mg/kg) once daily during five days before LPS (0.1 mg/kg, intraperitoneal). TNF-alpha was measured by cytotoxicity on L-929 cells. One hour after LPS injection, a significant mean increase of TNF-alpha in mouse serum was observed. Ozone/oxygen gaseous mixture reduced serum TNF-alpha levels in a dose-dependent manner. Statistically significant decreases in TNF-alpha levels after LPS injection were observed either with ozone intraperitoneal applications at 0.2 (78 %), 0.4 (98.5 %) and 1.2 (98.6 %) mg/ kg or by rectal application at 0.2 (46.2 %) and 0.4 (97.4 %) mg/kg. These results indicate that ozone oxidative preconditioning inhibits TNF-alpha production.